Drug therapy for hypertension in the elderly.

Essential hypertension is a major health care problem in the elderly and requires effective treatment to reduce morbidity and mortality. The traditional stepped-care approach to therapy consisted of diuretics; sympatholytic agents, or beta-blockers for all age groups. Indeed, initial therapy with these agents is effective in 50 to 60 percent of elderly patients but may produce adverse effects. A high incidence of adverse responses, including sexual dysfunction and central nervous system impairment, has been reported with diuretic or beta-blocker therapy, and a reduction in several measures of quality of life has been noted during therapy with methyldopa or propranolol. Administration of an angiotensin-converting enzyme (ACE) inhibitor is as effective as the traditional stepped-care approach without producing the ill effects associated with diuretics, sympatholytics, or beta-blockers. The combination of an ACE inhibitor with a diuretic produces additive antihypertensive effects while minimizing diuretic-induced metabolic alterations. Orthostatic hypotension with the first dose can be minimized by making sure that patients are not hypovolemic from previous diuretic therapy. Nevertheless, in controlled trials, the combination of ACE inhibitor and diuretic has been effective in up to 85 percent of patients. In addition, the use of ACE inhibitors may be beneficial in the hypertensive patient with concomitant congestive heart failure. Most important, the patient's quality of life is maintained during therapy with an ACE inhibitor alone or in combination with a diuretic. Thus, an ACE inhibitor plus a diuretic is a valuable alternative to traditional antihypertensive therapy in elderly patients.

Cefuroxime axetil and penicillin V compared in the treatment of group A beta-hemolytic streptococcal pharyngitis.

Patients with the signs and symptoms of acute tonsillopharyngitis were treated with cefuroxime axetil, an orally administered, beta-lactamase stable cephalosporin, or penicillin V for ten days. Group A beta-hemolytic streptococcal (GABHS) infection was confirmed bacteriologically in 115 patients. Patients aged 13 to 18 years received 250 mg of cefuroxime or 500 mg of penicillin V twice daily. Bacteriologic cure was found in 33 (94%) of 35 patients treated with the cefuroxime and in 12 (67%) of 18 treated with penicillin (P less than 0.05). Patients aged 4 to 12 years who received 125 mg of cefuroxime axetil twice daily also experienced a greater rate of bacteriologic cure than patients who received 250 mg of penicillin V three times daily, but the difference was not statistically significant. Cefuroxime axetil is at least as effective as penicillin V in the management of streptococcal pharyngitis and may be more effective in preventing the carrier state.

Compliance of neonatal nurse practitioners with gentamicin pharmacokinetic recommendations.

The compliance of nurse practitioners in a neonatal intensive-care center with gentamicin dosage recommendations from a pharmacokinetic consultation service was determined. Medical and pharmacokinetic dosage data were collected retrospectively from the medical records and pharmacokinetic consultation records of eligible neonates as soon as they had completed gentamicin therapy. Neonates for whom pharmacokinetic dosage recommendations had been followed by each of four neonatal nurse practitioners (NNPs) were compared with neonates for whom recommendations had not been followed to identify patient characteristics that might have influenced NNP compliance with the recommendations. Each NNP also completed a questionnaire designed to elicit information about professional and behavioral characteristics that might be associated with compliance. Data were collected for a total of 98 neonates. Discriminant analysis revealed no significant differences between the two groups of neonates. Although the NNPs perceived themselves to be in high compliance with the pharmacokinetic recommendations, the actual group compliance rate was 43%. Neonatal nurse practitioners may require special education in the proper use of pharmacokinetic dosage recommendations even if they perceive themselves to be compliant with those recommendations.

Use of ticarcillin disodium plus clavulanate potassium in the management of acute bacterial infections in children.

Ticarcillin disodium plus clavulanate potassium (in a ratio of 30:1) was used to treat 30 children (mean age equal to 4.9 years) with acute infections of the urinary tract, skeletal system, respiratory tract, gastrointestinal tract, skin and subcutaneous tissue, and blood. The drug was administered by the intravenous or intramuscular route in a dose of 310 mg/kg per day in six divided doses (26 patients) or 207 mg/kg per day in four divided doses (four patients). Duration of therapy ranged from two to 14 days (mean equal to 5.4 days), and resolution of infection was quite satisfactory in all cases, including those involving beta-lactamase-producing bacteria, although reinfection occurred five days after successful therapy of a urinary tract infection due to Escherichia coli. No adverse clinical or biochemical changes attributable to administration of ticarcillin disodium plus clavulanate potassium were observed. Ticarcillin disodium plus clavulanate potassium appears to be safe and effective therapy for a wide range of acute infections in children, including those caused by at least some pathogens that produce beta-lactamase.

Effect of erythromycin stearate on serum theophylline concentration in patients with chronic obstructive lung disease.

The effect of erythromycin stearate (ES) on serum theophylline concentration (STC) was studied in 15 male adult subjects taking maintenance oral theophylline for clinically stable chronic obstructive lung disease. Steady-state trough STCs were measured before and after two- and seven-day courses of ES, 500 mg every six hours. For the group as a whole, there was no significant increase in trough STC after either course of ES therapy, but five of 15 subjects exhibited increases in trough STC ranging from 4 to 8 micrograms/ml (mean increase of 5.4 micrograms/ml) within 48 to 96 hours of beginning ES therapy. Clinical theophylline toxicity developed in one of these subjects. Based on this study and others in the literature, erythromycin preparations may induce a clinically significant and potentially toxic increase in STC in a variable proportion of patients taking maintenance theophylline therapy.

Stimulation of endogenous catecholamine release by theophylline: a proposed additional mechanism of action for theophylline effects.

Therapeutic response to theophylline in asthma is generally attributed to its effect in increasing intracellular 3',5' cyclic adenosine monophosphate (cAMP) by competitive inhibition of cAMP phosphodiesterase. However, because of discrepancies between therapeutic serum theophylline concentration achieved clinically and those required for in vitro phosphodiesterase inhibition, we explored the possibility that theophylline may act through adrenomedullary secretion of catecholamines. Five healthy, nonasthmatic male and female adults were studied with a double-blind, randomized, crossover protocol. Theophylline (5 mg/kg) and placebo were administered in a capsule dosage form. Plasma catecholamines epinephrine (E), norepinephrine (NE), and dopamine (DA) were measured by a radioenzymatic assay at baseline and after administration of theophylline at 1, 2, and 3 hr. Significant differences between theophylline- and placebo-treated groups (p less than 0.05) were seen at 3 hr for mean percentage increase over baseline with E (120% +/- 25.3%) and NE (48.02% +/- 17.94%) after theophylline therapy (mean peak level 7.2 +/- 0.48 micrograms/ml). Epinephrine plasma concentration was significantly greater (p less than 0.001) at 3 hr compared with baseline (105 +/- 16 vs 56 +/- 18 pg/ml), while NE (448 +/- 52 vs 320 +/- 36 pg/ml) did not attain significance (p = 0.136). A significant correlation (p less than 0.05) was found between the percentage increase over basal for E (r = 0.58) and NE (r = 0.66) and serum theophylline levels. DA was not significantly increased at any time period. Thus theophylline in clinically relevant concentration appears to stimulate adrenomedullary secretion of catecholamine. Whether this is an important mechanism of action in asthma or explains some side effects of theophylline remains to be determined.

The use of an antihistamine-decongestant in conjunction with an anti-infective drug in the treatment of acute otitis media.

We evaluated the efficacy of an antihistamine-decongestant combination as adjunctive therapy in the treatment of acute otitis media with effusion. In a randomized study, 53 children were treated for acute otitis media with antibiotics and either Naldecon or placebo. Subjects were evaluated by tympanometry and pneumotoscopy. Follow-up evaluation was performed at days seven and 14 of therapy. The antihistamine-decongestant prescription was found to influence both the duration of nasal congestion and the course of middle ear effusion: Naldecon-treated subjects were symptomatic with nasal congestion for an average of six days compared to nine days reported by those given placebo, and the risk of persisting middle ear effusion was approximately two times greater in the placebo-treated group when evaluated by tympanometry.